Abstract
Aims
To evaluate hyaluronan expression at different stages of tumoral progression in primary breast cancer.
Methods
Hyaluronan expression was evaluated by histochemical techniques in 42 cases of pure DCIS, in 15 cases of DCIS with a microinvasive component, and in 32 cases of invasive ductal carcinoma of the breast. Staining results were evaluated by calculating the percentage of stained areas by means of a specific software program.
Results
Our results show higher values of hyaluronan expression in invasive breast carcinomas [median of percentage of stained areas 41.1 (range 8–69.2)] and in DCIS with a microinvasive component [48.6 (16.8–62.8)] than in pure DCIS [14.5 (1–44.4)] (p < 0.001, for both).
Conclusions
Our study indicates a proportionally higher area of hyaluronan expression in DCIS with a microinvasive component than in pure DCIS, suggesting a key role of this glycosaminoglycan in the early invasive phase of breast carcinomas. Thus, hyaluronan could play an important function in determining the migratory phenotype of cancer cells. Larger size tumors appear to demonstrate an intricate balance between hyaluronan synthesis and degradation, thus conditioning intratumoral heterogeneity in the hyaluronan metabolism.
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References
Arai H, Kang KY, Sato H et al (1979) Significance of the quantification and demonstration of hyaluronic acid in tissue specimens for the diagnosis of pleural mesothelioma. Am Rev Respir Dis 120:529–532
Auvinen P, Tammi R, Parkkinen J et al (2000) Hyaluronan in peritumoral stroma and malignant cells associates with breast cancer spreading and predicts survival. Am J Pathol 156:529–536
Bertrand P, Girard N, Delpech B et al (1992) Hyaluronan (hyaluronic acid) and hyaluronectin in the extracellular matrix of human breast carcinomas: comparison between invasive and non-invasive areas. Int J Cancer 52:1–6
Brown CT, Applebaum E, Banwatt R et al (1995) Synthesis of stromal glycosaminoglycans in response to injury. J Cell Biochem 59:57–68
Catterall JB, Jones LM, Turner GA (1999) Membrane protein glycosylation and CD44 content in the adhesion of human ovarian cancer cells to hyaluronan. Clin Exp Metastasis 17:583–591
Consensus Conference (1997) Consensus conference on the classification of ductal carcinoma in situ. Hum Pathol 28:1221–1225. doi:10.1016/S0046-8177(97)90193-3
Corte MD, Gonzalez LO, Lamelas ML et al (2006) Expression and clinical signification of cytosolic hyaluronan levels in invasive breast cancer. Breast Cancer Res Treat 97:329–337
de la Torre M, Wells AF, Bergh J et al (1993) Localization of hyaluronan in normal breast tissue, radial scar, and tubular breast carcinoma. Hum Pathol 24:1294–1297
Elston EW, Ellis IO (1993) Method for grading breast cancer. J Clin Pathol 46:189–190
Entwistle J, Hall CL, Turley EA (1996) HA receptors: regulators of signalling to the cytoskeleton. J Cell Biochem 61:569–577
Fraser JR, Laurent TC, Laurent UB (1997) Hyaluronan: its nature, distribution, functions and turnover. J Intern Med 242:27–33
Goebeler M, Kaufmann D, Brocker E et al (1996) Migration of highly aggressive melanoma cells on hyaluronic acid is associated with functional changes, increased turnover and shedding of CD44 receptors. J Cell Sci 109(Pt 7):1957–1964
Hopwood JJ, Dorfman A (1978) Glycosaminoglycan synthesis by Wilms’ tumor. Pediatr Res 12:52–56
Knudson W, Biswas C, Toole BP (1984) Interactions between human tumor cells and fibroblasts stimulate hyaluronate synthesis. Proc Natl Acad Sci USA 81:6767–6771
Kosunen A, Ropponen K, Kellokoski J et al (2004) Reduced expression of hyaluronan is a strong indicator of poor survival in oral squamous cell carcinoma. Oral Oncol 40:257–263
Koyama H, Hibi T, Isogai Z et al (2007) Hyperproduction of hyaluronan in neu-induced mammary tumor accelerates angiogenesis through stromal cell recruitment: possible involvement of versican/PG-M. Am J Pathol 170:1086–1099
Llaneza A, Vizoso F, Rodriguez JC et al (2000) Hyaluronic acid as prognostic marker in resectable colorectal cancer. Br J Surg 87:1690–1696
Ponting J, Howell A, Pye D et al (1992) Prognostic relevance of serum hyaluronan levels in patients with breast cancer. Int J Cancer 52:873–876
Prehm P (1984) Hyaluronate is synthesized at plasma membranes. Biochem J 220:597–600
Rooney P, Kumar S, Ponting J et al (1995) The role of hyaluronan in tumour neovascularization (review). Int J Cancer 60:632–636
Rudzki Z, Jothy S (1997) CD44 and the adhesion of neoplastic cells. Mol Pathol 50:57–71
Setala LP, Tammi MI, Tammi RH et al (1999) Hyaluronan expression in gastric cancer cells is associated with local and nodal spread and reduced survival rate. Br J Cancer 79:1133–1138
Sowa M, Kato Y, Nishimura M et al (1989) Clinico-histochemical studies on type 4 carcinoma of the stomach—with special reference to mucopolysaccharides and sialic acid in tumor tissue. Jpn J Surg 19:153–162
Sugahara KN, Murai T, Nishinakamura H et al (2003) Hyaluronan oligosaccharides induce CD44 cleavage and promote cell migration in CD44-expressing tumor cells. J Biol Chem 278:32259–32265
Suwiwat S, Ricciardelli C, Tammi R et al (2004) Expression of extracellular matrix components versican, chondroitin sulfate, tenascin, and hyaluronan, and their association with disease outcome in node-negative breast cancer. Clin Cancer Res 10:2491–2498
Takeuchi J, Sobue M, Sato E et al (1976) Variation in glycosaminoglycan components of breast tumors. Cancer Res 36:2133–2139
Toole BP (1990) Hyaluronan and its binding proteins, the hyaladherins. Curr Opin Cell Biol 2:839–844
Toole BP (2004) Hyaluronan: from extracellular glue to pericellular cue. Nat Rev Cancer 4:528–539
Tzircotis G, Thorne RF, Isacke CM (2005) Chemotaxis towards hyaluronan is dependent on CD44 expression and modulated by cell type variation in CD44-hyaluronan binding. J Cell Sci 118:5119–5128
Udabage L, Brownlee GR, Nilsson SK et al (2005a) The over-expression of HAS2, Hyal-2 and CD44 is implicated in the invasiveness of breast cancer. Exp Cell Res 310:205–217
Udabage L, Brownlee GR, Waltham M et al (2005b) Antisense-mediated suppression of hyaluronan synthase 2 inhibits the tumorigenesis and progression of breast cancer. Cancer Res 65:6139–6150
UK National Coordinating Group for Breast Cancer Screening Pathology (1995) Pathology reporting in breast cancer screening, 2nd edn. NHSBSB Publications, Sheffield
Vizoso FJ, del Casar JM, Corte MD et al (2004) Significance of cytosolic hyaluronan levels in gastric cancer. Eur J Surg Oncol 30:318–324
Wang C, Tammi M, Guo H et al (1996) Hyaluronan distribution in the normal epithelium of esophagus, stomach, and colon and their cancers. Am J Pathol 148:1861–1869
Wernicke M, Pineiro LC, Caramutti D et al (2003) Breast cancer stromal myxoid changes are associated with tumor invasion and metastasis: a central role for hyaluronan. Mod Pathol 16:99–107
Zhang L, Underhill CB, Chen L (1995) Hyaluronan on the surface of tumor cells is correlated with metastatic behavior. Cancer Res 55:428–433
Acknowledgments
Supported by grants from FIS-PI040137, Fondo de Inversión Sanitaria del Instituto Carlos III (FIS-Spain), and Obra Social Cajastur.
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We declare that we have no conflict of interest.
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Corte, M.D., González, L.O., Junquera, S. et al. Analysis of the expression of hyaluronan in intraductal and invasive carcinomas of the breast. J Cancer Res Clin Oncol 136, 745–750 (2010). https://doi.org/10.1007/s00432-009-0713-2
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DOI: https://doi.org/10.1007/s00432-009-0713-2